tbuckley/cabot-search huggingface dataset:
18F-Fluciclovine PET/CT
Authors: Charles Marcus, David M. Schuster, Shahein Holmes Tajmir
Journal: Clinical Nuclear Medicine (2022)

Abstract Incidental concomitant second primary malignancy may be detected on PET/CT imaging. We present an 18 F-fluciclovine PET/CT of a patient undergoing evaluation of biochemically recurrent prostate cancer with incidental radiotracer uptake within lytic osseous lesions confirmed to be multiple myeloma. We present the 18 F-fluciclovine PET/CT images of an 83-year-old man with prostate cancer treated in 2005 who presented with back pain and a CT scan revealing multiple lytic osseous lesions concerning for metastases versus a plasma cell neoplasm. Prostate-specific antigen at the time of evaluation was 0.1 ng/mL.
18F-FDG PET/CT Findings of MALT Lymphoma of Ureter
Authors: Limeng He, Yujiao Deng, Ying Deng, Hongjun Xie, Wei Zhang
Journal: Clinical Nuclear Medicine (2022)

Abstract Mucosa-associated lymphoid tissue (MALT) lymphoma origin from the ureter is exceedingly rare. We report FDG PET/CT findings of MALT lymphoma in the distal right ureter in a 55-year-old woman who presented right abdominal pain for 10 days. Ultrasound revealed a hypoechoic mass in the right pelvis, which was surrounding the distal right ureter. 18 F-FDG PET/CT demonstrated a high FDG uptake by the mass along with several FDG-avid enlarged lymph nodes in the abdominal cavity. Postoperative pathology demonstrated the ureteral mass as a MALT lymphoma.
Melanin-Targeted PET Imaging Sheds Light on Pigment Epithelioma in Corpus Ciliare
Authors: Xiao Zhang, Mengting Li, Fan Hu, Xiaoli Lan
Journal: Clinical Nuclear Medicine (2022)

Abstract A 57-year-old woman had gradually decreased visual acuity in the left eye, accompanied by distension and pain. MRI demonstrated a small neoplasm in corpus ciliare, which promoted PET imaging for further assessment. 18 F-FDG PET imaging found no obvious uptake in the lesion. However, melanin-targeted PET imaging demonstrated the lesion with avid 18 F-PFPN ( 18 F- N -(2-diethylaminoethyl)-4-(2-[2-ethoxy]-ethoxy)pyridine) accumulation (SUVmax, 7.1), which suggested it with melanin expression. Pigmented epithelial adenoma was further confirmed by pathology. Our case illustrated that pigmented epithelial adenoma is characterized by avid 18 F-PFPN accumulations and can be detected even in a hidden location with a size of ≤5 mm.
Re: Matthew Mossanena, Filipe L.F. Carvalhoa, Vinayak Muralidhar, et al. Genomic Features of Muscle-invasive Bladder Cancer Arising After Prostate Radiotherapy. Eur Urol 2022;81:466–73
Authors: Yuxuan Song, Yiqing Du, Tao Xu
Journal: European Urology (2022)
Dynamic degradation patterns of porous polycaprolactone/β-tricalcium phosphate composites orchestrate macrophage responses and immunoregulatory bone regeneration
Authors: Hao Wu, Xinghui Wei, Yichao Liu, Hui Dong, Zhen Tang, Ning Wang, Shusen Bao, Zhigang Wu, Lei Shi, Xiongfei Zheng, Xiaokang Li, Zheng Guo
Journal: Bioactive Materials (2022)

Biodegradable polycaprolactone/β-tricalcium phosphate (PT) composites are desirable candidates for bone tissue engineering applications. A higher β-tricalcium phosphate (TCP) ceramic content improves the mechanical, hydrophilic and osteogenic properties of PT scaffolds in vitro. Using a dynamic degradation reactor, we established a steady in vitro degradation model to investigate the changes in the physio-chemical and biological properties of PT scaffolds during degradation.PT46 and PT37 scaffolds underwent degradation more rapidly than PT scaffolds with lower TCP contents. In vivo studies revealed the rapid degradation of PT (PT46 and PT37) scaffolds disturbed macrophage responses and lead to bone healing failure. Macrophage co-culture assays and a subcutaneous implantation model indicated that the scaffold degradation process dynamically affected macrophage responses, especially polarization. RNA-Seq analysis indicated phagocytosis of the degradation products of PT37 scaffolds induces oxidative stress and inflammatory M1 polarization in macrophages. Overall, this study reveals that the dynamic patterns of biodegradation of degradable bone scaffolds highly orchestrate immune responses and thus determine the success of bone regeneration. Therefore, through evaluation of the biological effects of biomaterials during the entire process of degradation on immune responses and bone regeneration are necessary in order to develop more promising biomaterials for bone regeneration.
Lubricant skin on diverse biomaterials with complex shapes via polydopamine-mediated surface functionalization for biomedical applications
Authors: Kijun Park, Seunghoi Kim, Yejin Jo, Jae Park, Inwoo Kim, Sooyoung Hwang, Yeontaek Lee, So Yeon Kim, Jungmok Seo
Journal: Bioactive Materials (2022)

Implantable biomedical devices require an anti-biofouling, mechanically robust, low friction surface for a prolonged lifespan and improved performance. However, there exist no methods that could provide uniform and effective coatings for medical devices with complex shapes and materials to prevent immune-related side effects and thrombosis when they encounter biological tissues. Here, we report a lubricant skin (L-skin), a coating method based on the application of thin layers of bio-adhesive and lubricant-swellable perfluoropolymer that impart anti-biofouling, frictionless, robust, and heat-mediated self-healing properties. We demonstrate biocompatible, mechanically robust, and sterilization-safe L-skin in applications of bioprinting, microfluidics, catheter, and long and narrow medical tubing. We envision that diverse applications of L-skin improve device longevity, as well as anti-biofouling attributes in biomedical devices with complex shapes and material compositions.
89Zr-panitumumab Combined With 18F-FDG PET Improves Detection and Staging of Head and Neck Squamous Cell Carcinoma
Authors: Yu-Jin Lee, Nynke S. van den Berg, Heying Duan, E. Carmen Azevedo, Valentina Ferri, Marisa Hom, Roan C. Raymundo, Alex Valencia, Jessa Castillo, Bin Shen, Quan Zhou, Laura Freeman, Mary Ellen Koran, Michael J. Kaplan, A. Dimitrios Colevas, Fred M. Baik, Frederick T. Chin, Brock A. Martin, Andrei Iagaru, Eben L. Rosenthal
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Determine the safety and specificity of a tumor-targeted radiotracer (89Zr-pan) in combination with 18F-FDG PET/CT to improve diagnostic accuracy in head and neck squamous cell carcinoma (HNSCC). Experimental Design: Adult patients with biopsy-proven HNSCC scheduled for standard-of-care surgery were enrolled in a clinical trial and underwent systemic administration of 89Zirconium-panitumumab and panitumumab-IRDye800 followed by preoperative 89Zr-pan PET/CT and intraoperative fluorescence imaging. The sensitivity, specificity, and AUC were evaluated. Results: A total of fourteen patients were enrolled and completed the study. Four patients (28.5%) had areas of high 18F-FDG uptake outside the head and neck region with maximum standardized uptake values (SUVmax) greater than 2.0 that were not detected on 89Zr-pan PET/CT. These four patients with incidental findings underwent further workup and had no evidence of cancer on biopsy or clinical follow-up. Forty-eight lesions (primary tumor, LNs, incidental findings) with SUVmax ranging 2.0–23.6 were visualized on 18F-FDG PET/CT; 34 lesions on 89Zr-pan PET/CT with SUVmax ranging 0.9–10.5. The combined ability of 18F-FDG PET/CT and 89Zr-pan PET/CT to detect HNSCC in the whole body was improved with higher specificity of 96.3% [confidence interval (CI), 89.2%–100%] compared to 18F-FDG PET/CT alone with specificity of 74.1% (CI, 74.1%–90.6%). One possibly related grade 1 adverse event of prolonged QTc (460 ms) was reported but resolved in follow-up. Conclusions: 89Zr-pan PET/CT imaging is safe and may be valuable in discriminating incidental findings identified on 18F-FDG PET/CT from true positive lesions and in localizing metastatic LNs.
Association of Newborn Telomere Length With Blood Pressure in Childhood
Authors: Dries S. Martens, Hanne Sleurs, Yinthe Dockx, Leen Rasking, Michelle Plusquin, Tim S. Nawrot
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Adult telomere length (TL) is a biological marker of aging associated with vascular health. TL at birth is associated with later life TL and may contain early biological information of later life cardiovascular health and disease. <h3>Objective</h3> To evaluate whether newborn TL is associated with early life blood pressure differences in childhood. <h3>Design, Setting, and Participants</h3> This cohort study was part of the ENVIRONAGE (Environmental Influence on Aging in Early Life) study, a birth cohort of Belgian mother-child pairs with recruitment at birth and a median follow-up of 4.5 years conducted between October 2014 and July 2021. Participants included for analysis provided full data for evaluation at follow-up visit. Data analysis was conducted between August and September 2021. <h3>Main Outcomes and Measures</h3> Cord blood and placental average relative TL were measured at birth using quantitative polymerase chain reaction (qPCR). Systolic, diastolic, and mean arterial pressure (MAP) were evaluated at follow-up. High childhood blood pressure (standardized for child age, sex, and height) was defined following the 2017 American Academy of Pediatrics guidelines. Multivariable adjusted linear and logistic regression models were used to associate newborn TL and blood pressure indicators in childhood. <h3>Results</h3> This study included 485 newborn children (52.8% girls) with a mean (SD) age of 4.6 (0.4) years at the follow-up visit. Newborn TL was associated with lower blood pressure in childhood. A 1-IQR increase in cord blood TL was associated with a –1.54 mm Hg (95% CI, –2.36 to –0.72 mm Hg) lower diastolic blood pressure and –1.18 mm Hg (95% CI, –1.89 to –0.46 mm Hg) lower MAP. No association was observed with systolic blood pressure. Furthermore, a 1-IQR increase in cord blood TL was associated with lower odds of having high blood pressure at the age of 4 to 6 years (adjusted OR, 0.72; 95% CI, 0.53 to 0.98). In placenta, a 1-IQR increase in TL was associated with a –0.96 mm Hg (95% CI, –1.72 to –0.21 mm Hg) lower diastolic, –0.88 mm Hg (95% CI, –1.54 to –0.22 mm Hg) lower MAP, and a lower adjusted OR of 0.69 (95% CI, 0.52 to 0.92) for having a high blood pressure in childhood. <h3>Conclusions and Relevance</h3> In this prospective birth cohort study, variation in early life blood pressure at school-age was associated with TL at birth. Cardiovascular health may to some extent be programmed at birth, and these results suggest that TL entails a biological mechanism in this programming.
Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy
Authors: Shivani Handa, Jeong-Ok Lee, Andriy Derkach, Richard M. Stone, Alan Saven, Jessica K. Altman, Michael R. Grever, Kanti R. Rai, Madhulika Shukla, Shreya Vemuri, Skye Montoya, Justin Taylor, Omar Abdel-Wahab, Martin S. Tallman, Jae H. Park
Journal: Blood (2022)
An Immunogenic Model of KRAS-Mutant Lung Cancer Enables Evaluation of Targeted Therapy and Immunotherapy Combinations
Authors: Jesse Boumelha, Sophie de Carné Trécesson, Emily K. Law, Pablo Romero-Clavijo, Matthew A. Coelho, Kevin W. Ng, Edurne Mugarza, Christopher Moore, Sareena Rana, Deborah R. Caswell, Miguel Murillo, David C. Hancock, Prokopios P. Argyris, William L. Brown, Cameron Durfee, Lindsay K. Larson, Rachel I. Vogel, Alejandro Suárez-Bonnet, Simon L. Priestnall, Philip East, Sarah J. Ross, George Kassiotis, Miriam Molina-Arcas, Charles Swanton, Reuben Harris, Julian Downward
Journal: Cancer Research (2022)

Abstract Mutations in oncogenes such as KRAS and EGFR cause a high proportion of lung cancers. Drugs targeting these proteins cause tumor regression but ultimately fail to elicit cures. As a result, there is an intense interest in how to best combine targeted therapies with other treatments, such as immunotherapies. However, preclinical systems for studying the interaction of lung tumors with the host immune system are inadequate, in part due to the low tumor mutational burden in genetically engineered mouse models. Here we set out to develop mouse models of mutant KRAS–driven lung cancer with an elevated tumor mutational burden by expressing the human DNA cytosine deaminase, APOBEC3B, to mimic the mutational signature seen in human lung cancer. This failed to substantially increase clonal tumor mutational burden and autochthonous tumors remained refractory to immunotherapy. However, establishing clonal cell lines from these tumors enabled the generation of an immunogenic syngeneic transplantation model of KRAS-mutant lung adenocarcinoma that was sensitive to immunotherapy. Unexpectedly, antitumor immune responses were not directed against neoantigens but instead targeted derepressed endogenous retroviral antigens. The ability of KRASG12C inhibitors to cause regression of KRASG12C -expressing tumors was markedly potentiated by the adaptive immune system, highlighting the importance of using immunocompetent models for evaluating targeted therapies. Overall, this model provides a unique opportunity for the study of combinations of targeted and immunotherapies in immune-hot lung cancer. Significance: This study develops a mouse model of immunogenic KRAS-mutant lung cancer to facilitate the investigation of optimal combinations of targeted therapies with immunotherapies.
A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study)
Authors: Feng Wang, Ming-Ming He, Jian Xiao, Yan-Qiao Zhang, Xiang-Lin Yuan, Wei-Jia Fang, Yan Zhang, Wei Wang, Xiao-Hua Hu, Zhi-Gang Ma, Yi-Chen Yao, Zhi-Xiang Zhuang, Fu-Xiang Zhou, Jie-Er Ying, Ying Yuan, Qing-Feng Zou, Zeng-Qing Guo, Xiang-Yuan Wu, Ying Jin, Zong-Jiong Mai, Zhi-Qiang Wang, Hong Qiu, Ying Guo, Si-Mei Shi, Shuang-Zhen Chen, Hui-Yan Luo, Dong-Sheng Zhang, Feng-Hua Wang, Yu-Hong Li, Rui-Hua Xu
Journal: Clinical Cancer Research (2022)

Abstract Purpose: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). Patients and Methods: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription. Results: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70–1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50–0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. Conclusions: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.
mvPPT: A Highly Efficient and Sensitive Pathogenicity Prediction Tool for Missense Variants
Authors: Shi-Yuan Tong, Ke Fan, Zai-Wei Zhou, Lin-Yun Liu, Shu-Qing Zhang, Yinghui Fu, Guang-Zhong Wang, Ying Zhu, Yong-Chun Yu
Journal: Genomics Proteomics & Bioinformatics (2022)

Next-generation sequencing technologies both boost the discovery of variants in the human genome and exacerbate the challenges of pathogenic variant identification. In this study, we developed Pathogenicity Prediction Tool for missense variants (mvPPT), a highly sensitive and accurate missense variant classifier based on gradient boosting. mvPPT adopts high-confidence training sets with a wide spectrum of variant profiles, and extracts three categories of features, including scores from existing prediction tools, frequencies (allele frequencies, amino acid frequencies, and genotype frequencies), and genomic context. Compared with established predictors, mvPPT achieves superior performance in all test sets, regardless of data source. In addition, our study also provides guidance for training set and feature selection strategies, as well as reveals highly relevant features, which may further provide biological insights into variant pathogenicity. mvPPT is freely available at http://www.mvppt.club/.
SARS-CoV-2 Infections and Presymptomatic Type 1 Diabetes Autoimmunity in Children and Adolescents From Colorado, USA, and Bavaria, Germany
Authors: Marian Rewers, Ezio Bonifacio, Dominik Ewald, Cristy Geno Rasmussen, Xiaofan Jia, Laura Pyle, Anette-Gabriele Ziegler
Journal: JAMA (2022)

This study screens more than 50 000 youths in diverse populations of Colorado and Bavaria to assess whether previous SARS-CoV-2 infection was associated with autoimmunity, which predicts future type 1 diabetes.
Suspected Interstitial Lung Disease in COPDGene Study
Authors: Jonathan A. Rose, Aravind A. Menon, Takuya Hino, Akinori Hata, Mizuki Nishino, David A. Lynch, Ivan O. Rosas, Souheil El-Chemaly, Benjamin A. Raby, Samuel Y. Ash, Bina Choi, George R. Washko, Edwin K. Silverman, Michael H. Cho, Hiroto Hatabu, Rachel K. Putman, Gary M. Hunninghake
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Although interstitial lung abnormalities (ILA), specific patterns of incidentally-detected abnormal density on computed tomography, have been associated with abnormal lung function and increased mortality, it is unclear if a subset with incidental interstitial lung disease (ILD) accounts for these adverse consequences.
<i>Escherichia coli</i>–Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer
Authors: Anne-Gaëlle Goubet, Leonardo Lordello, Carolina Alves Costa Silva, Isabelle Peguillet, Marianne Gazzano, Maxime Descartes Mbogning-Fonkou, Cassandra Thelemaque, Cédric Lebacle, Constance Thibault, François Audenet, Géraldine Pignot, Gwenaelle Gravis, Carole Helissey, Luca Campedel, Morgan Roupret, Evanguelos Xylinas, Idir Ouzaid, Agathe Dubuisson, Marine Mazzenga, Caroline Flament, Pierre Ly, Virginie Marty, Nicolas Signolle, Allan Sauvat, Thomas Sbarrato, Mounia Filahi, Caroline Davin, Gabriel Haddad, Jacques Bou Khalil, Camille Bleriot, François-Xavier Danlos, Garett Dunsmore, Kevin Mulder, Aymeric Silvin, Thibault Raoult, Baptiste Archambaud, Shaima Belhechmi, Ivo Gomperts Boneca, Nadège Cayet, Maryse Moya-Nilges, Adeline Mallet, Romain Daillere, Etienne Rouleau, Camelia Radulescu, Yves Allory, Jacques Fieschi, Mathieu Rouanne, Florent Ginhoux, Gwénaël Le Teuff, Lisa Derosa, Aurélien Marabelle, Jeroen Van Dorp, Nick Van Dijk, Michiel S. Van Der Heijden, Benjamin Besse, Fabrice Andre, Miriam Merad, Guido Kroemer, Jean-Yves Scoazec, Laurence Zitvogel, Yohann Loriot
Journal: Cancer Discovery (2022)

Abstract Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Profiling tumor and blood samples, we found that follicular helper CD4+ T cells (TFH) are among the best therapeutic targets of pembrolizumab correlating with progression-free survival. TFH were associated with tumoral CD8 and PD-L1 expression at baseline and the induction of tertiary lymphoid structures after pembrolizumab. Blood central memory TFH accumulated in tumors where they produce CXCL13, a chemokine found in the plasma of responders only. IgG4+CD38+ TFH residing in bladder tissues correlated with clinical benefit. Finally, TFH and IgG directed against urothelium-invasive Escherichia coli dictated clinical responses to pembrolizumab in three independent cohorts. The links between tumor infection and success of ICB immunomodulation should be prospectively assessed at a larger scale. Significance: In patients with bladder cancer treated with neoadjuvant pembrolizumab, E. coli–specific CXCL13 producing TFH and IgG constitute biomarkers that predict clinical benefit. Beyond its role as a biomarker, such immune responses against E. coli might be harnessed for future therapeutic strategies. This article is highlighted in the In This Issue feature, p. 2221
Long-Term Outcomes After Transplantation for Acute Myelogenous Leukemia
Authors: Gerard Socie
Journal: Journal of Clinical Oncology (2022)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology, to patients seen in their own clinical practice.Hematopoietic stem-cell transplantation (HSCT) has been used for more than four decades as consolidation therapy in acute myelogenous leukemia (AML). Allogeneic HSCT is almost universally used today, and autologous HSCT nearly disappeared from daily practice. Improvement in transplantation strategies, supportive care, and increased donor source availability led to increased numbers of long-term survivors after HSCT. In the accompanying paper of this ground rounds, Armenian and coworkers analyzed the burden of late complications after HSCT for AML in a large cohort of patients and compared severe/life-threatening conditions with those of siblings. This study reinforces the need for prolonged clinical follow-up of transplanted patients otherwise nearly cured of their original disease for late malignant and nonmalignant complications.
Effectiveness of Varenicline and Cytisine for Alcohol Use Reduction Among People With HIV and Substance Use
Authors: Hilary A. Tindle, Matthew S. Freiberg, Debbie M. Cheng, Natalia Gnatienko, Elena Blokhina, Tatiana Yaroslavtseva, Sally Bendiks, Gregory Patts, Judith Hahn, Kaku So-Armah, Michael D. Stein, Kendall Bryant, Dmitry Lioznov, Evgeny Krupitsky, Jeffrey H. Samet
Journal: JAMA Network Open (2022)

Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking but are unproven for alcohol, and clinical trials rarely include individuals with HIV, substance use, and mental health conditions.